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Diamond Light Source is to build a dedicated electron diffraction instrument for drug discovery research, as part of a larger collaboration grant from Wellcome that has been awarded to The Rosalind Franklin Institute, with partners MRC Laboratory of Molecular Biology (MRC LMB) and Diamond. The £25m grant will support the development of three new electron imaging technologies that will have the capacity to revolutionise how we see life. Diamond’s share of the grant will fund the development of HeXI, a Hybrid electron - X-ray Instrument set to play a major role in drug discovery efforts.
Collectively known as ‘Electrifying Life Science’, the electron imaging technologies will create globally unique capabilities for the UK. The overall project will be led by Professor James Naismith, Director of The Franklin, Professor David Stuart, Director of Life Sciences at Diamond, and Dr Richard Henderson, group leader at the MRC LMB. Together, the team will change by a factor of ten the accessibility and capability of electron cryomicroscopy (cryo-EM), in both tomography and single particle sub-fields.
HeXI will be a dedicated electron diffraction instrument embedded within Diamond’s VMXm micro/nano focus X-ray beamline facility. When combined with X-ray methods, it will enable crystallography on small crystals ranging from around 100 nm, approximately 100 times thinner than a human hair, to up to 10 µm (ten millionths of a metre). Upon completion, HeXI will be accessible through the Diamond user programme.
Dr Gwyndaf Evans, a Diamond and Franklin group leader and leader of the HeXI project, said:
HeXI will combine and build upon state-of-the-art technologies from electron and X-ray fields to create brand new scientific opportunities for structural biology and drug discovery. It will make electron diffraction easily accessible to all of Diamond’s existing life science users and attract new users to routinely study pharmaceutical compounds and their binding.
Professor Dave Stuart, adds:
It is fantastic to work alongside The Franklin and MRC LMB on this exciting project, which will make pioneering electron imaging techniques more widely available. It is a great demonstration of how we can collaborate with other organisations on the Harwell Campus to harness the complementary scientific capabilities and expertise we have right here on our doorstep. This grant will enable us to push the boundaries of imaging in life science.
The Franklin will lead on the Amplus project, an instrument that will be built at The Franklin Hub and which will deliver a revolution in cryo-electron tomography – using electron microscopy to build up three dimensional models inside the cell. This will bring into view the possibility of imaging whole cells at atomic scale quickly and accurately. The team say that there are huge technical challenges to overcome in cryo-electron tomography, from sample milling, handling, and imaging, plus data reconstruction. However, they are clear that the pay-off from accomplishing these technical challenges will be enormous, with applications in genetic disease, intracellular pathogens, understanding the mechanisms of microbial drug resistance, and observing viral infection. To make the process robust and accessible, automation will be built into every step, from sample handling to data processing.
Technology developed with MRC LMB will democratise access to electron cryomicroscopy. Working with the technique’s pioneer and Nobel Prize winner, Dr Richard Henderson, and LMB group leader Dr Chris Russo, the team will develop instrumentation to enable single particle cryo-EM at 100 keV, as opposed to industry standard 200 and 300 keV machines with no loss of quality in resolution. This reduction in energy drives down the cost of equipment, and reduces the environmental requirements of the microscopes, taking the technique out of highly specialist spaces and into everyday laboratories. This democratisation will enable specialist labs to undertake more complex work, raising the standards of cryo-EM across the board.
Commenting on the overall project, Professor James Naismith, said:
This high-risk, high-reward multidisciplinary project is what the UK Government set up The Rosalind Franklin Institute to do. I cannot emphasise enough the teamwork required to get us to this stage and how important it will be going forward. Electrifying Life Science will be a true factor of ten change in our ability to see and understand life. We are incredibly grateful to Wellcome for placing their trust in us. I want to acknowledge additional funding from UKRI-EPSRC, core funding partners of The Franklin, and of course from our industrial partners who are contributing their world leading engineering and design capability. Everyone at The Franklin feels humbled by this and are excited to start work to deliver on our promises.
Dr Tom Collins, interim Head of Genetics & Molecular Sciences at Wellcome, said:
There has been an explosion in the scientific impact of cryo-electron microscopy since the introduction of revolutionary electron detector technology. We are excited about this project that gives us an opportunity to bring closer together structural and cell biology through the development of the next generation of this innovative technology.
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
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